Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands.
Department of Clinical Genetics, Erasmus MC, University Medical Center, 3015 CN Rotterdam, The Netherlands.
Int J Mol Sci. 2023 Mar 7;24(6):5097. doi: 10.3390/ijms24065097.
Secretin-stimulated pancreatic juice (PJ), collected from the duodenum, presents a valuable biomarker source for the (earlier) detection of pancreatic cancer (PC). Here, we evaluate the feasibility and performance of shallow sequencing to detect copy number variations (CNVs) in cell-free DNA (cfDNA) from PJ for PC detection. First, we confirmed the feasibility of shallow sequencing in PJ (n = 4), matched plasma (n = 3) and tissue samples (n = 4, microarray). Subsequently, shallow sequencing was performed on cfDNA from PJ of 26 cases (25 sporadic PC, 1 high-grade dysplasia) and 19 controls with a hereditary or familial increased risk of PC. 40 of the 45 PJ samples met the quality criteria for cfDNA analysis. Nine individuals had an 8q24 gain (oncogene MYC; 23%; eight cases (33%) and one control (6%), = 0.04); six had both a 2q gain (STAT1) and 5p loss (CDH10; 15%; four cases (7%) and two controls (13%), = 0.72). The presence of an 8q24 gain differentiated the cases and controls, with a sensitivity of 33% (95% CI 16-55%) and specificity of 94% (95% CI 70-100%). The presence of either an 8q24 or 2q gain with a 5p loss was related to a sensitivity of 50% (95% CI 29-71%) and specificity of 81% (95% CI 54-96%). Shallow sequencing of PJ is feasible. The presence of an 8q24 gain in PJ shows promise as a biomarker for the detection of PC. Further research is required with a larger sample size and consecutively collected samples in high-risk individuals prior to implementation in a surveillance cohort.
从十二指肠采集的促胰液素刺激的胰液 (PJ) 是一种有价值的生物标志物来源，可用于（更早地）检测胰腺癌 (PC)。在这里，我们评估了对 PJ 中的游离细胞 DNA (cfDNA) 进行浅层测序以检测 PC 检测中的拷贝数变异 (CNV) 的可行性和性能。首先，我们在 PJ (n = 4)、匹配的血浆 (n = 3) 和组织样本 (n = 4，微阵列) 中证实了浅层测序的可行性。随后，对 26 例病例 (25 例散发性 PC，1 例高级别发育不良) 和 19 例遗传性或家族性 PC 风险增加的对照者的 PJ 中的 cfDNA 进行了浅层测序。45 个 PJ 样本中有 40 个符合 cfDNA 分析的质量标准。9 个人有 8q24 增益（癌基因 MYC；23%；8 例 (33%) 和 1 例对照 (6%)，= 0.04)；6 人既有 2q 增益（STAT1）又有 5p 缺失（CDH10；15%；4 例 (7%) 和 2 例对照 (13%)，= 0.72)。8q24 增益的存在可区分病例和对照，其敏感性为 33%（95%CI 16-55%），特异性为 94%（95%CI 70-100%）。PJ 中存在 8q24 或 2q 增益和 5p 缺失与敏感性为 50%（95%CI 29-71%）和特异性为 81%（95%CI 54-96%）相关。PJ 的浅层测序是可行的。PJ 中 8q24 增益的存在有望成为检测 PC 的生物标志物。在实施于监测队列之前，需要进行更大样本量的研究，并在高危人群中连续采集样本。
